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Interpenetrating polymeric hydrogels as favorable materials for hygienic applications

Ahmed M. Khalil 1, *

1Photochemistry Department, National Research Centre, El-Buhouth St., Dokki - 12622, Giza, Egypt

*corresponding author e-mail address: akhalil75@yahoo.com | Scopus ID: 55605778944

ABSTRACT

Polymers can crosslink to produce intermingled materials with three-dimensional network structure known as interpenetrating polymeric

network (IPN). They comprise elastic crosslinked polymeric chains. The chains of the hydrogels are either physically or chemically

entangled together. Interpenetrating hydrogels can be tailored to provide enhanced materials. They can be classified according to

methods of their synthesis as simultaneous or sequential IPNs and the structure to be homo or semi IPNs. The preparation factors play a

role in controlling the properties of the produced IPNs. Moreover, the ambient conditions such as pH, temperature as well as the ionic

strength may affect the performance of these hydrogels. The swelling capacity is an important feature that allows the prepared hydrogel

to perform the required application. Some disadvantages may arise such as the low mechanical properties that are suggested to be

overcome. IPNs can be used in various applications that serve the human requirements like drug delivery, tissue engineering, medical

and packaging applications. Hydrogels present biocompatibility and nontoxicity when used in biomedical applications. Interpenetrating

hydrogels can be prepared from natural or synthetic polymers. Polysaccharides as natural polymers can be used to produce efficient

interpenetrating hydrogels. Polyacrylates, poly(ethylene glycol) and poly(vinyl alcohol) are designated as promising synthetic polymers

capable of forming interpenetrating hydrogels.

Keywords: Interpenetrating polymeric network; hydrogel; medical application; tissue engineering, food packaging.

1. INTRODUCTION

Interpenetrating polymers are crosslinked materials

composed of two or more polymers. They are intermingled partly

without covalent bonds. Hydrogels are polymers with three-

dimensional network structure. This structure detaches when the

chemical bonds are cracked. Interpenetrating polymeric network

(IPN) has the ability to swell in water. Upon swelling, these

polymers are elastic and smooth like living tissue. They can be

employed in controlled release applications. This can be supported

by their low toxicity, biocompatibility and facile dispersion in the

medium they are used in. Different natural or synthesized

hydrogels are used in drug delivery and pharmaceutical products

and heavy metal removal [1-4]. Chitosan is a natural polymer

derived from chitin. It is a successful and common polymer used

in such applications. Hydrogels can be formed chemically stable

polymers known as physical gels. This kind is heterogeneous.

They result from an interaction between two oppositely charged

polyelectrolytes. These gels may degrade by altering the

surrounding conditions including the temperature, pH and ionic

strength of the solution as well. They can be employed in

biomedical implementations such as wound dressing and drug

delivery [5-7]. Meanwhile, chemical gels are produced from

covalently crosslinked networks. These hydrogels can be

categorized as single network hydrogels. Some disadvantages may

arise such as their feeble mechanical properties which have to be

overcome. Various hydrogels may face the problem of weak

mechanical properties after prolonged use in aqueous media.

Reinforcing agents are used to enhance the mechanical strengths

of these gels [8,9]. Polymer hydrogels are composed of elastic

crosslinked networks. They have liquid filling interspaces. They

are able to alter their shape and volume and shape with respect to

the surrounding conditions such as temperature and pH of their

hosting media [10-12]. The response of IPNs may take place either

by swelling, shrinking or bending features. Interpenetrating

polymeric network (IPN) can be assorted as illustrated in Figure 1;

referring to: i) Methods of their synthesis to be: a) Simultaneous

IPN; where the parent components are polymerized at the same

time. b) Sequential IPN; that takes place by swelling a hydrogel in

a medium loaded with monomer, initiator in absence or in the

presence of crosslinker as a polymeric network is formed followed

by the formation of the other [13-15]. ii) The structure to be: a)

Homo-IPN where two polymers have the same structure produce

two different networks. b) Semi-IPN is composed of a crosslinked

polymer with a linear one. The structures of IPN and semi-IPN are

shown in Figure 2.

Figure 1. Schematic illustration for the classification of interpenetrating

polymeric network hydrogels.

Cellulose, chitosan and chitin as well as their derivatives as

natural polysaccharides are used widely in industrial and medical

implications. They are safe, biodegradable with specific structures.

Carboxymethyl cellulose and carboxymethyl chitosan are

cellulose and chitosan derivatives; respectively [16,17]. They are

used utilized in pharmaceutical, food, and metal ions removal

[18,19]. These natural polymers are blended with natural and

Volume 10, Issue 2, 2020, 5011 - 5020 ISSN 2069-5837

Open Access Journal Received: 05.12.2019 / Revised: 18.01.2020 / Accepted: 22.01.2020 / Published on-line: 27.01.2020

Original Review Article

Biointerface Research in Applied Chemistry www.BiointerfaceResearch.com

https://doi.org/10.33263/BRIAC102.011020

Ahmed M. Khalil

Page | 5012

synthetic polymers to show high adsorption abilities as metal

adsorbents. The behavior of these hydrogel in metal ions

adsorption was controlled by the composition of each blend. The

pH-sensitive chitosan hydrogel sustains drug delivery in the

stomach. It swells in acidic media. This results from protonating

their free NH2 groups [20-22]. Chitosan/alginate polymers as pH-

sensitive hydrogels are used in biomedical implications [23,24].

These polymers were developed to produce a crosslinked semi-

interpenetrating polymeric network (semi-IPN) hydrogel.

Protecting peptide and protein drugs has to be considered as they

have to be conserved from the acidic medium of the stomach

before absorption in the intestine [25]. IPNs can contribute to

delivering these drugs safely to the required site safely. Semi-

interpenetrating network hydrogels (semi-IPN) of chitosan and

polyacrylonitrile, crosslinked with glutaraldehyde were prepared

in different compositions. These semi-IPNs as temperature and

pH-sensitive gels showed comparatively high swelling capacity

upon increasing the chitosan amount [26,27]. Interpenetrating

polymeric network is known as a mixture of two polymers. One of

them is synthesized or crosslinked in the presence of the other one

[28]. This can be achieved by preparing monomers solution with

an initiator. IPN is able to get control of thermodynamic

incompatibility resulting from the interlocking of polymeric

network. However, restricted phase separation may occur with

maintaining the morphological features [29-31]. Producing IPNs

has merit of having robust hydrogel network with stiff mechanical

properties. The physical properties can be tailored to show higher

loading efficiency when compared to conventional hydrogels [32].

Interpenetrating hydrogels demonstrate various degradation

stages. They may differ in the swelling capacities as they are able

to be employed in supplying variable swelling response of

hydrogels in the drug release kinetics [33,34]. IPNs are capable of

restraining the environmental changes that can affect their

behavior including their swelling and elasticity. It was reported

that crosslinked interpenetrating hydrogels show sensitivity, i.e.

the swelling capacity may change at different pH values [35,36].

This response may reduce the burst release of drugs in oral

implications. Crosslinked interpenetrating hydrogel based on

chitosan and poly(N-isopropylacrylamide) network showed a

significant increase in the loading capacity of diclofenac compared

to sole poly(N-isopropylacrylamide) hydrogel. The thermal

sensitivity of the polymer was maintained with regular release

kinetics [37]. Modified polyethylene glycol diacrylate gels with β-

chitosan showed enhanced biocompatibility. This hydrogel was

prepared via mixing aqueous solution of polyethylene glycol

diacrylate with a solution of chitosan in acetic acid. This was

followed by induced ultraviolet (UV) crosslinking. IPN hydrogels

of polyurethane and polyacrylamide are capable of monitoring

water absorption [38,39]. These aforementioned polymers were

mingled together, then crosslinked after exposure to UV radiation.

The prepared interpenetrating hydrogels are commonly employed

as wound dressing substrates, biosensors and artificial muscles as

well.

Figure 2. a) Two different polymers. b) Semi-interpenetrating polymer

network. c) Interpenetrating polymer network.

Interpenetrating calcium alginate with dextran-hydroxy-ethyl

methacrylate-derivative is considered as an in-situ formed

polysaccharide hydrogel [40,41]. The prepared IPN hydrogel was

designed for protein releasing and to monitor the behavior of

embedded cells. The results proposed that these IPNs are

promising candidates for pharmaceutical and biomedical

applications. This originates from their convenient mechanical and

degradation characteristics and biocompatibility. Polysaccharide

hydrogel [42] based on calcium alginate and dextran methacrylate

derivative reflected successful features for this hydrogel to be used

in pharmaceutical applications. The distribution of dextran-

acrylate chains inside the calcium alginate hydrogel evolved

superior rheological properties than those of calcium alginate. This

facilitates the way to inject this semi-IPN easily through

hypodermic needle. UV Curing the semi-IPN [43,44] leads to

crosslinking. Hence, this hydrogel is robust enough to deliver

bioactive molecules such as proteins.

2. PROPERTIES OF HYDROGELS

Hydrogels are supposed to be favorable materials for use in

pharmaceutical industry and biomedical applications. They can be

functionalized as drug carriers because of their biocompatibility

and nontoxicity. To estimate the efficiency of these materials, their

characteristic properties have to be evaluated in order to rely upon

these hydrogels upon application.

2.1. Swelling behavior.

The chains of the hydrogels are either physically or

chemically entangled. Hence they are taken into consideration as

one molecule; i.e. large molecules or super macromolecules. Some

variations in the ambient conditions are able to cause rapid and

reversible changes in hydrogels. The changes in the surrounding

conditions as temperature, pH of the medium or the presence of

ionic species may vary the physical structure and the volume of

the hydrogel. The extent of ionization for the functional groups

contributes to the swelling behavior and the generated changes in

the volume. Polyacrylic acid is a pH sensitive hydrogel [45,46].

The swelling behavior varies according to the ionization of

carboxyl groups in the polymeric chains. Some hydrogels based

on poly(N-isopropylacrylamide) were investigated. The

fluorescence of these hydrogels was influenced by the crosslinker

and monomer concentrations. The thermal response these

hydrogels was affected by copolymerization of N-

Isopropylacrylamide with the hyrophilic N,N-dimethylacrylamide

monomer and methyl methacrylate as a hydrophobic monomer

[47].

2.2. Mechanical properties.

The mechanical properties of hydrogels are essential ones

to be investigated from the biomedical perspective. This

application comprises wound dressing, tendon repair, tissue

Interpenetrating polymeric hydrogels as favorable materials for hygienic applications

Page | 5013

engineering and cartilage replacement. The mechanical properties

of hydrogels have to preserve the physical texture of therapeutics.

Raising the degree of crosslinking of a stronger hydrogel may lead

to decreasing the percentage elongation with a brittle hydrogel.

IPNs show a covalently crosslinked network. Ionically crosslinked

gels were prepared to explore the efficient factors able to monitor

the physical and mechanical properties interpenetrating hydrogels.

The mechanical properties are highly affected by the blending

ratio of the components. Some modifiers and compatibilizers can

be used to improve the mechanical properties of interpenetrating

gels. Physical crosslinking may restrict some mechanical

properties. Covalently crosslinked gels, may supply many featured

advantages, comprising controlled gel formation and degradation.

Moreover, potent mechanical properties may arise permitting

superior gel loading. Copolymerizing a hydrogel with monomer

via hydrogen bonding can support in reaching optimum

mechanical properties [48,49].

2.3. Biocompatibility of IPNs.

Hydrogels are supposed to show biocompatibility and

nontoxicity to be employed in biomedical applications. For these

materials to be biocompatible, they have to act as a suitable host

for the enclosing tissues and biofunctional materials so as to be

capable of carrying out certain functions. In tissue engineering

application, it is important that tissues can be generated by

continuous interaction with the body. This takes place upon

healing and cellular regeneration step. Upon polymerizing

synthetic hydrogels, some hazardous compounds may exist. They

have to be totally removed to obtain a safe and biocompatible

hydrogel. Among the troubles regarding the hydrogel toxicity, the

unreacted monomers and initiators are mentioned. It is essential to

estimate the toxicity of the hydrogel components such as

monomers and initiators [50]. To get rid of the toxic chemicals,

purification step has to be done with consecutive washing.

Preparing hydrogels without initiators may reduce the risk of

having toxic hydrogels. Poly(vinyl alcohol) hydrogels were

prepared via freeze-thawing method in an attempt to reduce

toxicity. The formed crystals presented physical crosslinks. They

are able to resist the exerted load on the hydrogels. Poly(ethylene

glycol)-poly(epsilon-caprolactone)-poly (ethylene glycol)

copolymer was synthesized [51]. The toxicity of the hydrogel as

an efficient material in drug delivery system was investigated. The

biodegradation of the hydrogel was evaluated in ophthalmic uses.

The results showed promising biocompatibility and toxicity

significance. Natural polymers have the privilege to be

biocompatible when compared to synthetic ones. They can ensure

possessing safe ingredients with high performance upon being

used in specific applications. For investigating the compatibility of

tissue after being implanted, in-vitro cell culture assays known as

cytotoxicity tests have to be undertaken. These investigations are

utilized to estimate the biocompatibility of the hydrogels

comprising elution, direct contact and agar diffusion [52-54]. The

alterations that may arise in cell morphology were monitored.

Evaluating the tissue compatibility of a hydrogel is performed

with perceiving the chemical composition of the biomaterial.

Moreover, the criteria of exposing the tissue exposure such as

nature, degree and duration of exposure have to be taken into

consideration.

3. CHARACTERIZATION OF IPNs

3.1. IPN hydrogels based on natural polymers.

Polysaccharides as natural polymers are employed as

successful materials for building up IPN hydrogels. Chitosan is a

linear polysaccharide is formed from acetylated and deacetylated

glucosamine units. By the high content of amino and hydroxyl

functional groups, chitosan acts efficiently in adsorbing dyes and

heavy metal ions [55-58], due to comprising NH2 and OH groups.

Chitosan drew the attention to be used in designing potent drug

delivery materials [59-62]. The preparation of hydrogels

composed of polyethylene glycol grafted on carboxymethyl

chitosan and alginate has been investigated. An improvement in

the protein release at a certain pH was monitored. This proposed

that the prepared hydrogel is effective for protein intestinal drug

delivery [63]. Chitosan and its derivatives were utilized to produce

IPN composite hydrogels with different polymers possessing

carboxylic groups such as poly(acrylic acid) [64-66], poly(N-

acryloylglycine) and poly(methacrylic acid) [22,67-69]. Preparing

semi-IPN was attained by selective crosslinking of chitosan in the

presence of a polyelectrolyte [70-72] or by the synthesis of the

crosslinked polyelectrolyte in the presence of chitosan [73,74].

Thermo- and pH-responsive semi-IPN polyampholyte hydrogels

based on carboxymethyl chitosan and methacrylate derivative [75]

drew attention. This hydrogel showed swelling as the pH departed

from the isoelectric point and exhibited shrinking at the

aforementioned point. Various IPN hydrogels were synthesized

via crosslinking polymerization of nonionic monomers with

chitosan. The commonly used monomers are acrylamide [76,77],

N-isopropylacrylamide [78,79], N,N-dimethylacrylamide [80,81]

and 2-hydroxyethyl methacrylate [82,83].

Cryogels are three dimensional flexible macroporous

polymeric gels. Their preparation takes place below the freezing

point of water (as a solvent) [84,85]. It is characteristic that

cryogels comprise interconnected macropores (with sizes between

1 and 100 m). This permits fast mass-transport of any solute

beside microparticles as well. These gels possess capillary

networks where the solvents flow by convective mass transport.

The osmotic stability allows these substrates to be convenient in

many materials for various biomedical applications and

bioseparations [86,87]. A unique character of cryogels is their

rapid swelling at equilibrium. They depend on the total monomer

concentration, the crosslinking density and polymerization

temperature. Both IPN and semi-IPN are pH responsive.

Meanwhile, IPN shows higher swelling kinetics than semi-IPN

cryogels. More time is important to attain the equilibrium swelling

due to the presence of two networks. They respond independently

with respect to surrounding variations. Sodium alginate is a linear

polysaccharide. It is derived from sea algae. It can crosslinks

easily. Sodium alginate is used excessively in foods, fabrics and

drug delivery systems [88]. Alginate based IPN are employed in

industrial applications as actuators. This results from their rapid

electric response with high mechanical strength. pH and thermo

responsive IPN hydrogels, consisting of sodium alginate and

poly(diallyl dimethyl ammonium chloride) were prepared [89]. At

pH range 2-6, the IPN hydrogels illustrated that the swelling rates

Ahmed M. Khalil

Page | 5014

increased with elevating the pH reaching a maxima at pH 4. This

resulted from an electrostatic repulsion upon ionizing the

carboxylic groups of alginate. An IPN based on sodium alginate

and poly(acrylamide) was prepared. It started with preparing

ionically crosslinked sodium alginate beads. It was soaked in the

solution of N-isopropyl acrylamide, crosslinker, and initiator. This

was followed by crosslinking polymerization [90]. The resulting

composite changed its transparency according to temperature

variations.

Starch is a widely used polysaccharide. It exhibits

advantageous features such as biodegradability, biocompatibility

and bioactivity. Starch granules are insoluble in water. Many

improvements were carried out with starch to enhance its

hydrophilic character [91]. Pristine and improved starches were

utilized as raw substrates to produce biodegradable hydrogels for

biomedical applications [92]. Amphoteric semi-IPN hydrogels

were synthesized via grafting acrylic acid on the surface of starch

in the presence of poly(methacryloyl oxyethyl ammonium

chloride) [93]. The swelling tests displayed a high swelling

capacity in distilled water. In other studies, potato starch was

modified with poly(acrylamide) [94]. The morphologies were

affected by the composition of the gels in addition to hydrolysis.

Hyaluronic acid; known as hyaluronan as it exists as polyanion, is

a linear hydrophilic polysaccharide of high molecular weight

consisting of glucuronic acid and glucosamine [95]. It is widely

used in tissue engineering and implanting materials applications. It

is able to adjust water balance to act as a lubricant by protecting

the cartilage's surface [96]. Among the disadvantages of

hyaluronic acid, its low stability is mentioned. This is due to its

high solubility in water. Some studies were performed to obtain

stable semi-IPN hydrogels based on hyaluronic acid with synthetic

polymers [96] or modified dextran [97]. The preparation

temperature has a role in determining the porous structure of the

networks. Thus, the network structures of the prepared semi-IPNs

showed a heterogeneous morphology consisting of interconnected

pores of various sizes. Besides, the stability of the prepared

hydrogels increased upon lowering the synthesis temperature by

elevating the crosslinker content.

3.2. IPN hydrogels based on synthetic polymers.

IPN hydrogels may be prepared from synthetic polymers.

They are designed and tailored with specific forms according to

the application they are going to be used in. IPN hydrogels based

on synthetic polymers can be classified into: a) IPN hydrogels

derived from nonionic synthetic polymers. The synthesis of semi-

IPN or IPN hydrogels depends mainly on poly(hydroxyl ethyl

methacrylate), polyethylene glycol, poly(acrylamide) and

poly(vinyl alcohol). These gels are employed mainly in separation

and biomedical implementations [98-100]. b) IPN hydrogels

derived from ionic synthetic polymers. These hydrogels include

anionic [101-103], cationic [104,105] and anionic/cationic

[106,107] polymers. The implicated linear polymer in semi-IPN

may change the sensitivity of the gels. The swelling kinetics of the

semi-IPN hydrogels is more rapid than that of the single-network

hydrogels. An irreversible breakdown of semi-IPN is presented.

The hydrogels did not retain their volume by reswelling after

shrinking [101]. Thermo-sensitive semi-IPN hydrogels were

developed by embedding poly(vinyl pyrrolidone) in poly(hydroxyl

ethyl methacrylate [108]. For enhancing the drug delivery of

hydrogels for hydrophobic drugs, semi-IPN hydrogels based on b-

cyclodextrin-epichlorohydrin in poly(3-acrylamidophenylboronic

acid-co-2-dimethyl aminoethyl methacrylate) were prepared [104].

The drug release was slower than in the corresponding

conventional hydrogel. This was affected by pH, temperature,

ionic strength and the glucose concentration. IPN hydrogels

possessing anionic and cationic groups in their chains stabilize by

ionic bonds beside covalent bonds. Polyion complexes may be

formed as IPN comprise particular ratios of adversely charged

groups. This leads to a promising category of functional substrates

that can be utilized in manufacturing drug delivery systems and

biomaterials. An IPN of poly(acrylic acid) and poly(vinyl amine)

were prepared. The proportion between anionic and cationic

groups was directed according to the amount of poly(acrylic acid).

3.3. IPN hydrogels based on proteins.

Different proteins were utilized to synthesize IPN

hydrogels mixed with either gelatin or synthetic polymers. The

aim of this process is to improve the blood biocompatibility of the

semi- IPN hydrogels. Polyethylene glycol diacrylate was used as a

crosslinker which goes through free radical crosslinking

polymerization without interacting with the functional groups of

gelatin. The resulting gel has improved structural stability in

aqueous solutions. Silk sericin is a water soluble protein derived

from silkworm. It was used to synthesized IPN hydrogels with

poly(N-isopropylacrylamide) [78] and poly(methyl methacrylate);

as a rapid pH-responsive hydrogel. Other protein based IPN

hydrogels are composed of fibrin with poly(ethylene glycol) or

hyaluronic acid [95] or soy protein [109]. Silk fibroin as a fibrous

protein with chains of connected polypeptides via disulfide was

utilized to prepare IPN hydrogels. The resulting fiber is a

promising material to be involved in biomaterials. This is due to

its reasonable mechanical strength in wet media. In addition, it is

biocompatible for implanting cells and resistant against enzymatic

disintegration. Poly(N-isopropylacrylamide) hydrogels show

acceptable mechanical properties with a slow deswelling rate.

Hence they can be used in tissue engineering and regenerative

medicine. This results from composing a skin layer. It opposes

releasing internal water molecules in the deswelling process which

is known as skin effect.

4. SOME APPLICATIONS FOR IPNs

4.1. Drug delivery applications.

IPNs of polysaccharides are nominated as efficient

materials for drug delivery implication. They possess high

mechanical properties when compared to single drug delivery

polymers. IPN based on methylcellulose and chitosan was

employed for controlled release of theophylline with an acceptable

antiasthmatic effect [110]. IPN gels were also synthesized from

carboxymethyl cellulose and kappa-carrageenan. Genipin was

used as a crosslinker to change the drug release process of beta-

carotene [111]. Egg white showed a novel IPN hydrogel when

blended with carboxymethyl cellulose coated with folic acid-egg

white. Cyclophosphamide was introduced to this gel as an

anticancer drug. This gel was utilized to treat breast cancer.

Releasing cyclophosphamide from folic acid/egg white

Interpenetrating polymeric hydrogels as favorable materials for hygienic applications

Page | 5015

cyclophosphamide (IPN-NPs) showed a fast release and pH

sensitivity pH 5 and 6 [112]. Poly(vinyl alcohol) was blended with

poly(acrylic acid) to produce IPN hydrogels. The swelling

capacity, thermal stability and biodegradability were investigated.

The prepared hydrogel demonstrated higher swelling at intestinal

pH than that of the stomach. The existence of NaCl in the

hydrophilic hydrogels boosted swelling behavior. The prepared

nontoxic gels showed promising results for drug delivery

applications referring to their swelling properties and

biodegradability [113].

4.2. Medical applications.

Interpenetrating hydrogels were used in some medical

applications mainly for neuronal applications. They were

employed in supporting neural stem cells. Signals to stem cell can

be reinforced by developing substrates able to coordinate these

signals. Efficient biomimetic IPNs can act as synthetic and

efficient stand for culturing adult neural stem cells. IPNs were

adjusted with cell-binding ligands from bone protein and laminin.

They were tested to regulate self-renewal and show the ability to

differentiate in dose dependency [114]. Various human neural

cells were cultured in different hydrogel 3D scaffolds. The results

illustrated that no single hydrogel exceeds the other hydrogels.

Collagen and hyaluronan with poly(vinyl alcohol) were mingled to

form an interpenetrating network (IPN) hydrogel. This IPN gel

merges cell supportiveness of the collagen gel with the stability of

the prepared hydrogel. The adhesion of neurons varies from that of

the fibroblasts. The results showed that the synthesized hydrogel

acts as a proper scaffold for neuronal cells [115]. Many humans

suffer from blindness as a result of corneal diseases. Treatment for

this problem may arise in the form of artificial corneal

transplantation. This can be obtained through tissue-engineered

corneas or synthetic corneal prostheses. Poly(ethylene glycol) and

poly(acrylic acid) IPNs were synthesized and molded. The

produced transparent hydrogel was removed softly from the mold.

It had a homogeneous and smooth texture. The prepared IPNs

showed good swelling properties. Their water content extended up

to 90% [116]. Artificial corneal scaffolds based on poly(vinyl

alcohol), silk fibroin and hydroxyapatite in the presence of genipin

as crosslinker were tailored to replace damaged cornea. This IPN

gel was a successful medical material to act as an alternate for

artificial cornea scaffold matrix. The physiological properties of

hydrogel were explored. The prepared hydrogels showed

promising physical features. The thermal stability and tensile

properties showed progress [117].

4.3. Tissue engineering application.

It is essential to synthesize scaffolds able to repair or

replace damaged tissues. Interpenetrating hydrogel networks can

be selected as promising materials with their three-dimensional

structure to be used as tissue engineering scaffolds for cell

encapsulation. This results from their high water content in

addition to being capable of imitating the native extracellular

material. Gelatin methacrylate and silk fibroin based IPN

hydrogels were synthesized and crosslinked to show structural and

biological properties. This study presented promising

photocrosslinkable IPN hydrogels. They have strong mechanical

properties and able to be used in tissue engineering applications

[118]. Biodegradable interpenetrating network hydrogels were

prepared from the gelatin and hyaluronic acid to resemble an

alternative for natural cartilage matrix. Poly(ethylene glycol)

diacrylate was blended with agarose to form a novel IPN hydrogel

with improved mechanical properties. The viability of these gels

was tested to show successful results. Encapsulating cells in these

hydrogels provided favorable alternatives to be used in repairing

disordered cartilages. This process may be employed to produce

different cell-based IPNs. This can be achieved by changing

monomers and their concentrations. In addition, introducing

functional groups may contribute to improving the properties of

these hydrogels [119].

4.4. Food packaging application.

Plastics are commonly used as convenient materials for

packaging purposes. This results from their availability at a low

cost. Moreover, they resist water and dirts with acceptable

mechanical, optical, thermal and barrier properties. The

disadvantages of using plastics are the difficulty in recycling them

besides being non-biodegradable materials. Interpenetrating

hydrogels can act as suitable alternatives for conventional plastics

in packaging implementations. Using interpenetrating hydrogels in

packaging applications allows the opportunity to generate

hydrogels from bio-based materials. This provides a favorable

approach to develop new biodegradable packaging materials. They

can be used in food packaging, as there is augmenting needs

towards having natural and environmentally compatible packaging

materials. Cellulose interpenetrating hydrogels show considerable

significance in biodegradable food packaging. Cellulose-based

hydrogels consist of cellulose and its derivatives. The

aforementioned materials can blend with gelatin, polyvinyl

pyrrolidone or polyvinyl alcohol to offer convenient packaging

food materials. Introducing bioactive substrates like silver

nanoparticles and antioxidants are able to improve the properties

of these hydrogel sheets [120]. Composites based on poly(vinyl

alcohol) and micro- and nano-fibrillated cellulose were prepared.

Inserting hydroxyethyl methacrylate with photo-initiator assisted

in producing an interpenetrated polymer network with improved

distribution and interfacial adhesion. The prepared IPN

composites presented enhanced materials for packaging

applications [121].

5. CONCLUSIONS

Interpenetrating polymeric network (IPN) hydrogels as

three-dimensional network polymers are either physically or

chemically entangled together. According to their classifications

either as simultaneous or sequential IPNs and the structure to be

homo or semi IPNs, they can be favored as promising materials

for hygienic applications. The preparation procedures influence

the properties of the produced IPNs. Hydrogels show

biocompatibility and nontoxicity when used in biomedical

applications. The swelling capacity is an important feature that

allows the prepared hydrogel to perform the required application.

Some disadvantages may arise such as the low mechanical

properties that are suggested to be overcome. IPNs can be used in

various applications that serve the human requirements like drug

delivery, tissue engineering, medical and packaging applications.

Ahmed M. Khalil

Page | 5016

Interpenetrating hydrogels can be prepared from natural or

synthetic polymers. For many years, interpenetrating hydrogels

invaded the medical and pharmaceutical fields. Nowadays many

drug dosages are delivered and working efficiently with the aid of

using IPNs. These hydrogels are based on natural polymers that

are favored as biocompatible and degradable materials. Some

IPNs and semi-IPNs are created by mixing natural with synthetic

polymers to generate novel hydrogels. The aforementioned

materials have superior mechanical and biomaterials with

enhanced rheological properties. This allows these gels to mimic

natural tissues with favorable performance to be used in tissue

engineering implications. Besides, IPNs act as successful materials

used in packaging applications.

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